Anticoagulation strategies in patients with atrial fibrillation after PCI or with ACS : The end of triple therapy?

Clinicians struggle daily with the optimal regimen for patients with an indication for antiplatelet therapy after stenting and in patients needing oral anticoagulation treatment for atrial fibrillation (AF). This is not only difficult in patients with acute coronary syndrome (ACS) but also in the large number of patients with AF undergoing elective percutaneous coronary intervention (PCI). The challenge is to strike a balance between the increasing risk of bleeding events and ischemic or thrombotic events. Until recently, guidelines were based on expert consensus and a few small, many of them retrospective, trials. A so-called triple therapy with a vitamin K antagonist (VKA) and dual antiplatelet therapy (DAPT) with aspirin and clopidogrel was recommended for patients with AF undergoing PCI in stable coronary artery disease or for those with ACS. However, severe bleeding complications remain a major issue during triple therapy, particularly in the growing aging population. In the past year, randomized controlled trials (RCT) with direct-acting oral anticoagulants (DOACs) have modified the standard use of care, now favoring dual therapy with DOACs. This review elucidates the current influential RCTs on the new antiplatelet and anticoagulation strategies for patients with AF undergoing PCI or with ACS, and discusses whether triple therapy is still required.

[Management of different cardiovascular risk factors with a combination tablet (polypill)]. / Management verschiedener kardiovaskulärer Risikofaktoren mit einem Kombinationspräparat ("Polypill").

BACKGROUND: The multifactorial origin of cardiovascular diseases has led to polypharmacy in primary and secondary prophylaxis with evidence-based medications, such as statins, antihypertensive drugs and platelet aggregation inhibitors. The number of prescribed drugs correlates inversely to adherence and can lead to treatment failure. Fixed-dose combination drugs (polypills) could increase the medication adherence of patients, reduce risks and prevent cardiovascular events. METHODS: This review is based on publications that were retrieved from Medline (via PubMed) and The Cochrane Library. The clinical database ClinicalTrials.gov. was also considered. RESULTS: In the studies on primary prevention conducted to date, fixed-dose combinations showed a superior control of risk factors, e.g. hypertension and low-density lipoprotein (LDL) cholesterol compared to placebo and at least non-inferiority compared to usual care. In secondary prevention, the effect of the polypill is mostly on the reduction of blood pressure and LDL cholesterol in non-adherent patients; however, evidence that fixed-drug combinations reduce cardiovascular morbidity and mortality compared to standard therapy is lacking. CONCLUSION: The polypill can be considered as an alternative to polypharmacy after a risk-benefit assessment, especially in non-adherent patients. Ongoing studies are investigating the effect of the polypill on cardiovascular events. Current polypills are limited by the lack of sufficient dosages of the individual components to avoid overtreatment and undertreatment at the individual treatment level.

Homocysteine concentration in coronary artery disease: Influence of three common single nucleotide polymorphisms.

BACKGROUND AND AIMS: Whether single nucleotide polymorphisms (SNPs) of homocysteine metabolism enzymes influence the rate of cardiovascular (CV) events in coronary artery disease (CAD) patients remains controversial. METHODS AND RESULTS: In this analysis, 1126 subjects from the AtheroGene study with CAD and 332 control subjects without known CAD were included. The following SNPs were investigated: methylentetrahydrofolate reductase (MTHFR-C667T), methionin synthetase (MS-D919G), and cystathionin beta synthetase (CBS-I278T). The endpoint was the combination of cardiovascular death, stroke, and non-fatal myocardial infarction (N = 286). The median follow-up time was 6.4 years. Kaplan-Meier curve analysis showed an increasing event rate with rising homocysteine levels (p < 0.001) in CAD patients. Further, in Cox-Regression analysis homocysteine was a predictor of the endpoint with a hazard ratio (HR) of 6.5 (95% CI: 2.9-14.6, p < 0.001) in the adjusted model including cardiovascular risk factors. Of the three SNPs, homozygous MTHFR SNP increased homocysteine levels significantly in patients with CAD and individuals without CAD (both p < 0.001). The SNPs in MS and CBS were not related to relevant changes in homocysteine levels in CAD patients or controls. The different SNPs of MTHFR, MS, and CBS were not related to an increased event rate. CONCLUSION: Homocysteine level is a strong predictor of CV events. Subjects with and without CAD and SNPs in the enzyme MTHFR had increased homocysteine levels. This was not observed for MS and CBS SNPs. Although MTHFR SNPs alter homocysteine levels in patients and controls, these polymorphisms had no impact on prognosis in CAD patients.

PDE2-mediated cAMP hydrolysis accelerates cardiac fibroblast to myofibroblast conversion and is antagonized by exogenous activation of cGMP signaling pathways.

Recent studies suggest that the signal molecules cAMP and cGMP have antifibrotic effects by negatively regulating pathways associated with fibroblast to myofibroblast (MyoCF) conversion. The phosphodiesterase 2 (PDE2) has the unique property to be stimulated by cGMP, which leads to a remarkable increase in cAMP hydrolysis and thus mediates a negative cross-talk between both pathways. PDE2 has been recently investigated in cardiomyocytes; here we specifically addressed its role in fibroblast conversion and cardiac fibrosis. PDE2 is abundantly expressed in both neonatal rat cardiac fibroblasts (CFs) and cardiomyocytes. The overexpression of PDE2 in CFs strongly reduced basal and isoprenaline-induced cAMP synthesis, and this decrease was sufficient to induce MyoCF conversion even in the absence of exogenous profibrotic stimuli. Functional stress-strain experiments with fibroblast-derived engineered connective tissue (ECT) demonstrated higher stiffness in ECTs overexpressing PDE2. In regard to cGMP, neither basal nor atrial natriuretic peptide-induced cGMP levels were affected by PDE2, whereas the response to nitric oxide donor sodium nitroprusside was slightly but significantly reduced. Interestingly, despite persistently depressed cAMP levels, both cGMP-elevating stimuli were able to completely prevent the PDE2-induced MyoCF phenotype, arguing for a double-tracked mechanism. In conclusion, PDE2 accelerates CF to MyoCF conversion, which leads to greater stiffness in ECTs. Atrial natriuretic peptide- and sodium nitroprusside-mediated cGMP synthesis completely reverses PDE2-induced fibroblast conversion. Thus PDE2 may augment cardiac remodeling, but this effect can also be overcome by enhanced cGMP. The redundant role of cAMP and cGMP as antifibrotic meditators may be viewed as a protective mechanism in heart failure.

Early results of a real-world series with two transapical transcatheter mitral valve replacement devices.

AIMS: Transcatheter mitral valve replacement (TMVR) with dedicated devices promises to fill the treatment gap between open-heart surgery and edge-to-edge repair for patients with severe mitral regurgitation (MR). We herein present a single-centre experience of a TMVR series with two transapical devices. METHODS AND RESULTS: A total of 11 patients were treated with the Tendyne™ (N = 7) or the Tiara™ TMVR systems (N = 4) from 2016 to 2020 either as compassionate-use procedures or as commercial implants. Clinical and echocardiographic data were collected at baseline, discharge and follow-up and are presented in accordance with the Mitral Valve Academic Research Consortium (MVARC) definitions. The study cohort [age 77 years (73, 84); 27.3% male] presented with primary (N = 4), secondary (N = 5) or mixed (N = 2) MR etiology. Patients were symptomatic (all NYHA III/IV) and at high surgical risk [logEuroSCORE II 8.1% (4.0, 17.4)]. Rates of impaired RV function (72.7%), severe pulmonary hypertension (27.3%), moderate or severe tricuspid regurgitation (63.6%) and prior aortic valve replacement (63.6%) were high. Severe mitral annulus calcification was present in two patients. Technical success was achieved in all patients. In 90.9% (N = 10) MR was completely eliminated (i.e. no or trace MR). Procedural and 30-day mortality were 0.0%. At follow-up NYHA class was I/II in the majority of patients. Overall mortality after 3 and 6 months was 10.0% and 22.2%. CONCLUSIONS: TMVR was performed successfully in these selected patients with complete elimination of MR in the majority of patients. Short-term mortality was low and most patients experienced persisting functional improvement.

[New oral anticoagulants: better than vitamin K antagonists?]. / Neue orale Antikoagulanzien: Werden sie die Vitamin-K-Antagonisten verdrängen?

Many years of practical use and intensive scientific research have allowed vitamin K antagonists to become a cornerstone of treatment of internal diseases. Nevertheless, limitations in pharmacokinetics and -dynamics of vitamin K antagonists and the availability of new drugs in regard to a targeted anticoagulation therapy ask for a new review of the situation. Proof of effectiveness for the perioperative prophylaxis of venous thrombosis after hip and knee replacement has already been achieved for the direct thrombin inhibitor dabigatran etexilate as well as for the factor Xa inhibitors rivaroxaban und apixaban compared to low molecular weight heparins. These new drugs are now also investigated in patients with internal diseases. For the long-term application (6 or 12 months) concerning the treatment of venous thrombosis and/or stroke prophylaxis in patients with atrial fibrillation data is already available for the direct thrombin inhibitor dabigatran etexilate. Depending on its dosage its effectiveness in comparison with vitamin K antagonists is equal or even better without disadvantages in safety. However, vitamin K antagonists will remain the standard oral anticoagulation until open questions regarding e.g. insufficient therapy adherence (with termination rates up to 20%) or problems with drug interactions of the new competitive products have been completely answered.

Biglycan is required for adaptive remodeling after myocardial infarction.

BACKGROUND: After myocardial infarction (MI), extensive remodeling of extracellular matrix contributes to scar formation and preservation of hemodynamic function. On the other hand, adverse and excessive extracellular matrix remodeling leads to fibrosis and impaired function. The present study investigates the role of the small leucine-rich proteoglycan biglycan during cardiac extracellular matrix remodeling and cardiac hemodynamics after MI. METHODS AND RESULTS: Experimental MI was induced in wild-type (WT) and bgn(-/0) mice by permanent ligation of the left anterior descending coronary artery. Biglycan expression was strongly increased at 3, 7, and 14 days after MI in WT mice. bgn(-/0) mice showed increased mortality rates after MI as a result of frequent left ventricular (LV) ruptures. Furthermore, tensile strength of the LV derived from bgn(-/0) mice 21 days after MI was reduced as measured ex vivo. Collagen matrix organization was severely impaired in bgn(-/0) mice, as shown by birefringence analysis of Sirius red staining and electron microscopy of collagen fibrils. At 21 days after MI, LV hemodynamic parameters were assessed by pressure-volume measurements in vivo to obtain LV end-diastolic pressure, end-diastolic volume, and end-systolic volume. bgn(-/0) mice were characterized by aggravated LV dilation evidenced by increased LV end-diastolic volume (bgn(-/0), 111+/-4.2 microL versus WT, 96+/-4.4 microL; P<0.05) and LV end-diastolic pressure (bgn(-/0), 24+/-2.7 versus WT, 18+/-1.8 mm Hg; P<0.05) and severely impaired LV function (EF, bgn(-/0), 12+/-2% versus WT, 21+/-4%; P<0.05) 21 days after MI. CONCLUSIONS: Biglycan is required for stable collagen matrix formation of infarct scars and for preservation of cardiac hemodynamic function.

Rational of the use of aliskiren in hypertension and beyond.

Arterial hypertension is an independent risk factor for cardiovascular diseases and one of the major causes for mortality worldwide. Drugs, that control hypertension effectively are therefore needed to reduce hypertension induced morbidity and mortality. The inhibition of the renin-angiotensin-aldosterone-system (RAAS) is one target to control blood pressure in these patients. The new direct renin inhibitor aliskiren is one new substance on the market to inhibit the RAAS effectively by suppression of the plasma renin activity, which inhibits the RAAS at its rate-limiting step. Therefore, aliskiren in monotherapy and in combination might yield beneficial effects for the patients. Nevertheless, blood pressure lowering has to be combined with a reduction of target organ damage for all drug classes prescribed to patients with hypertension. Therefore, we review here the major effects of this new drug not only in regard to hypertension but also in regard to target organ damage reduction and possible changes in morbidity and mortality, which future trials will investigate.

Treatment strategies for mixed aortic valve disease in nonelderly patients.

Introduction: Mixed aortic valve disease (MAVD) is defined by simultaneous occurrence of aortic stenosis (AS) and aortic regurgitation (AR). In our review, we focus on treatment options for nonelderly MAVD patients (age<55 years), who suffer from congenital aortic valve disease (unicuspid/bicuspid aortic valves).Areas covered: A systematic literature search was performed on PubMed and Embase databases using the following terms: mixed aortic valve disease, aortic stenosis/regurgitation, bicuspid/unicuspid aortic valve, mechanical/bioprosthetic aortic valve replacement, TAVR, Ross procedure. After preselection of title and abstracts, two authors (M.S. and E.G.) assessed the methodological quality of the full-text articles prior to final inclusion in the manuscript.Expert opinion: Currently, no ideal valvular substitutes are available in the treatment of nonelderly MAVD patients. Mechanical valves are associated with a reduced life expectancy due to a combination of prothesis-associated factors, mainly thrombotic and bleeding complications. Bioprostheses degenerate in the second decade and re-operations are inevitable, which also limit life expectancy. Long-term outcomes and durability of transcatheter aortic valve replacement are currently unknown. Finally, only Ross procedure is a therapeutic option with excellent long-term outcomes comparable to the healthy population. However, the Ross procedure has some important drawbacks and should therefore be only performed in expert centers and in well-selected patients.

Enhancement of endothelial nitric oxide synthase production reverses vascular dysfunction and inflammation in the hindlimbs of a rat model of diabetes.

AIMS/HYPOTHESIS: Reduced bioavailability of nitric oxide (NO) is a hallmark of diabetes mellitus-induced vascular complications. In the present study we investigated whether a pharmacological increase of endothelial NO synthase (eNOS) production can restore the impaired hindlimb flow in a rat model of severe diabetes. METHODS: A model of diabetes mellitus was induced in male Sprague-Dawley rats by a single injection of streptozotozin. Rats were treated chronically with the eNOS transcription enhancer AVE3085 (10 mg [kg body weight](-1) day(-1); p.o.) or vehicle for 48 days and compared with controls. Endothelial function and arterial BP were investigated in vivo using an autoperfused hindlimb model and TIP-catheter measurement, respectively. Protein production of eNOS, total and phosphorylated vasodilator-stimulated phosphoprotein (VASP) were assessed in their quadriceps muscle tissue, whereas cyclic GMP (cGMP) concentrations were assessed in blood plasma. RNA levels of intracellular and vascular cell adhesion molecules (ICAM-1 and VCAM-1) were measured by real-time PCR. RESULTS: Untreated diabetic rats showed significantly reduced quadriceps muscle contents of eNOS (-64%) and phosphorylated VASP (-26%) protein associated with impaired vascular function (maximum vasodilatation: -30%, p < 0.05) and enhanced production of ICAM-1 (+121%) and VCAM-1 (+156%). Chronic treatment with AVE3085 did not alter arterial BP or severe hyperglycaemia, but did lead to significantly increased production of eNOS (+95%), cGMP (+128%) and VASP phosphorylation (+65%) as well as to improved vascular function (+36%) associated with reduced production of ICAM-1 (-36%) and VCAM-1 (-58%). CONCLUSIONS/INTERPRETATION: In a rat model of severe diabetes, pharmacological enhancement of impaired eNOS production and NO-cGMP signalling by AVE3085 restores altered hindlimb blood flow and prevents vascular inflammation.

The cardiovascular influence of interleukin-1 beta on the expression of bradykinin B1 and B2 receptors.

The cytokine interleukin 1ss (IL-1ss) and the bradykinin receptors 1 (B1R) and 2 (B2R) are known to be upregulated in the ischemic heart. In the present study we investigated whether or not there is a causal link between these entities. Further we investigated whether or not pharmacological inhibition of IL-1ss release affects B1R and B2R regulation as well as left ventricular (LV) function in an in vivo rat model of myocardial infarction (MI). B1R and B2R mRNA levels were determined in cultured rat cardiomyocytes, aortic smooth muscle cells and cardiac fibroblasts (n=6 per group) under basal conditions, and after incubation of IL-1ss (40, 400 and 4000 pg/ml). Also, MI was induced in male Sprague-Dawley rats by ligation of the left descending coronary artery. Rats were treated with the interleukin converting enzyme inhibitor (ICEI) pralnacasan (50 mg/kg/day), or with a placebo. Three weeks after induction of MI, LV function was assessed using a 1.4 Millar TIP-catheter. Cardiac expressions of B1R and B2R mRNA were measured using ribonuclease-protection assays. Under basal conditions, both B1R and B2R were expressed in cardiomyocytes and smooth muscle cells, but not in cardiac fibroblasts. IL-1ss cultivation led only in cardiomyocytes to a significant upregulation of B1R mRNA. To a significant upregulation of B2R mRNA, it did not. In addition, ICEI treatment led in vivo to a significant downregulation of cardiac B1R mRNA, but not of B2R mRNA expression three weeks after induction of MI. Our data suggest that a causal link exists between cardiac IL-1ss content and B1R regulation after MI.

Cardiac overexpression of human VEGF(165) by recombinant Semliki Forest virus leads to adverse effects in pressure-induced heart failure.

Semliki Forest virus (SFV) is an efficient vector for cardiac gene delivery. The relatively short transgene expression induced by SFV seems appropriate for angiogenic gene therapy. We tested the effects of SFV expressing vascular endothelial growth factor (VEGF) on cardiac angiogenesis and heart failure in the mRen2 transgenic rat.Six-week-old mRen2 rats received SFV-VEGF or control virus (n=7 each) administered intracoronarily. Twelve days after transfection, cardiac capillary density and function were assessed. Capillary density in cardiac regions where SFV expression was highest had decreased by 20% in the SFV-VEGF-treated group. The decrease in capillary density was accompanied by impaired systolic function as illustrated by increased endsystolic volumes and a 34% decrease in cardiac output.We conclude that the time frame of SFV expression is sufficient to induce structural alterations, but that VEGF in mRen2 transgenic rats did not elicit the expected angiogenic effect. Rather, capillary density was decreased and subsequently cardiac function was impaired. This paradoxical finding is possibly related to the pathophysiology associated with this model and warrants caution if one is to pursue VEGF-mediated, angiogenic therapy before proceeding to a clinical setting. (Neth Heart J 2007;15:335-41.).

High prevalence of cardiac parvovirus B19 infection in patients with isolated left ventricular diastolic dysfunction.

BACKGROUND: The etiology of left ventricular (LV) isolated diastolic dysfunction often remains unclear. In the present study, we report a strong association between parvovirus B19 (PVB19) genomes and isolated LV diastolic dysfunction. METHODS AND RESULTS: In 70 patients (mean+/-SD age, 43+/-11 years) admitted with exertional dyspnea and/or reduced exercise tolerance despite preserved LV systolic contractility (ejection fraction=68%), isolated diastolic dysfunction was clinically suspected. Patients with classic risk factors for diastolic dysfunction such as hypertension, coronary heart disease, diabetes mellitus, or pulmonary disease had been excluded. Diastolic function was assessed by echocardiography and LV and RV catheterization. Endomyocardial biopsies (EMBs) were analyzed for the presence of storage or infiltrative diseases or myocarditis, including molecular screening for cardiotropic virus genomes. In a substudy of 24 patients who reported atypical angina, coronary endothelial function was additionally investigated with a coronary Doppler flow-wire technique. In 37 of 70 patients (53%), isolated diastolic dysfunction was confirmed as the cause of their clinical symptoms. No evidence for cardiac storage or infiltrative diseases was found in these cases, but in 35 of 37 of these patients (95%), cardiotropic virus genomes were detected in EMBs (P<0.001). PVB19 was the most frequent pathogen in 31 of 37 patients (84%). In a subgroup of 10 patients with diastolic dysfunction and coexisting endothelial dysfunction, all 10 (100%) were PVB19 positive. CONCLUSIONS: PVB19 genomes were predominant in patients with unexplained, isolated diastolic dysfunction. A strong association with the incidence of endothelial dysfunction was obvious, consistent with the hypothesis that PVB19-induced endothelial dysfunction may be a possible pathomechanism underlying diastolic dysfunction.

Sediment and phosphorus transport in irrigation furrows.

Sediment and phosphorus (P) in agricultural runoff can impair water quality in streams, lakes, and rivers. We studied the factors affecting P transfer and transport in irrigated furrows in six freshly tilled fallow fields, 110 to 180 m long with 0.007 to 0.012 m m-1 slopes without the interference of raindrops or sheet flow that occur during natural or simulated rain. The soil on all fields was Portneuf silt loam (coarse-silty, mixed, superactive, mesic Durinodic Xeric Haplocalcids). Flow rate, sediment concentration, and P concentrations were monitored at four, equally spaced locations in each furrow. Flow rate decreased with distance down the furrow as water infiltrated. Sediment concentration varied with distance and time with no set pattern. Total P concentrations related directly to sediment concentrations (r2=0.75) because typically >90% of the transported P was particulate P, emphasizing the need to control erosion to reduce P loss. Dissolved reactive phosphorus (DRP) concentrations decreased with time at a specific furrow site but increased with distance down the furrow as contact time with soil and suspended sediment increased. The DRP concentration correlated better with sediment concentration than extractable furrow soil P concentration. However, suspended sediment concentration tended to not affect DRP concentration later in the irrigation (>2 h). These results indicate that the effects of soil P can be overshadowed by differences in flow hydraulics, suspended sediment loads, and non-equilibrium conditions.

The predictive value of different equations for estimation of glomerular filtration rate in patients with coronary artery disease - Results from the AtheroGene study.

BACKGROUND: Impaired renal function leads to dramatically increased risk for the development and progression of coronary artery disease (CAD). Therefore we aimed to assess the predictive value of different equations for estimated glomerular filtration rate (eGFR) in CAD-patients. METHODS: From the AtheroGene study 2135 patients were included. eGFR was calculated using the 4-variable Modification of Diet in Renal Disease (4MDRD) equation for serum creatinine (sCr), the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for sCr and cystatin C (CysC) each alone, and in combination (CysC/sCr). eGFR was assessed regarding the combined outcome of cardiovascular death and non-fatal myocardial infarction and regarding complex CAD represented by a SYNTAX score ≥23. Median follow-up was 4.3years. RESULTS: Only the CKD-EPI equation using CysC could differentiate between eGFR >90ml/min/1.73m(2) vs. eGFR 60-90ml/min/1.73m(2) according to the occurrence of an endpoint event (log-rank test p=0.009). In the Cox regression analysis only eGFR calculated by CKD-EPI equation for CysC (Hazard ratio per 1 standard deviation (HR) 1.27 (95% CI 1.07-1.50); p=0.007) and for CysC/sCr (HR 1.22 (95% CI 1.02-1.46); p=0.026) were predictive regarding the outcome after adjustment for cardiovascular risk factors and Nt-proBNP. Furthermore, only eGFR calculated by CKD-EPI equation for CysC (odds ratio (OR) 1.57 (95% CI 1.36-1.78); p<0.001) and for CysC/sCr (OR 1.32 (95% CI 1.13-1.53); p<0.001) were significantly associated with a SYNTAX score ≥23. CONCLUSION: In patients with CAD the CKD-EPI equation for CysC and for CysC/sCr provided the best predictive value regarding the prognosis and the severity of CAD.

Aggravation of left ventricular dysfunction in patients with biopsy-proven cardiac human herpesvirus A and B infection.

BACKGROUND: Human herpesvirus 6 (HHV-6) A and B are lymphotropic viruses with life-long persistence, primarily associated with non-cardiac diseases, and discussed as a possible etiologic factor of myocarditis and cardiomyopathy. OBJECTIVE: To analyze the long-term spontaneous course of cardiac patients suffering from suspected inflammatory cardiomyopathy (CMi) with persisting HHV-6 A and B infections by follow-up biopsies. STUDY DESIGN: We prospectively evaluated patients (n=73) with biopsy-proven viral HHV-6 A and B infection in endomyocardial biopsies (EMBs), followed up by reanalysis of EMBs and left ventricular ejection fraction (LV-EF) measurements after a median period of 8.8 months (range 4-73 months). Beyond, we studied HHV-6 prevalence in isolated peripheral blood cells (PBCs) and HHV-6 species in EMBs. HHV-6 species-specific cellular infection sites within the myocardium were identified by immunohistochemistry (IHC). RESULTS: We identified 73 patients with cardiac HHV-6 A and B persistence or newly detected in follow-up EMB (95.0% B). Proof of HHV-6 in PBCs was primarily associated with A. Persistence of cardiac HHV-6 B genome was significantly associated with cardiac dysfunction at follow-up (LV-EF deteriorated from 58.2±16.0 to 51.8±17.2%, p<0.001), and LV improvement was observed when HHV-6 B persistence resolved (LV-EF increased from 54.9±15.4 to 60.7±13.1%, p<0.001). CONCLUSIONS: Persistence of cardiac HHV-6 B genomes was significantly associated with cardiac dysfunction, and hemodynamic parameters improved in association with HHV-6 B clearance.

Phosphorus runoff from two water sources on a calcareous soil.

Phosphorus (P) in irrigation runoff may enrich offsite water bodies and streams and be influenced by irrigation water quality and antecedent soil surface conditions. Runoff, soil loss, and P fractions in runoff using reverse osmosis (RO) water or mixed RO and well water (RO/ Tap) were studied in a laboratory sprinkler study to evaluate water source effects on P transport. A top- or subsoil Portneuf silt loam (coarse-silty, mixed, superactive, mesic Durinodic Xeric Haplocalcid), either amended or not amended with manure and/or with cheese whey, with Olsen P from 20 to 141 mg kg(-1) and lime from 108 to 243 g kg(-1), was placed in 1.5 x 1.2 x 0.2-m-deep containers with 2.4% slope and irrigated three times from a 3-m height for 15 min, applying 20 mm of water. The first irrigation was on a dry loose surface, the second on a wet surface, and the third on a dry crusted surface. Surface (ca. 2 cm) soil samples, prior to the first irrigation, were analyzed for Olsen P, water-soluble P (Pws), and iron-oxide impregnated paper-extractable P (FeO-P) analyses. Following each irrigation we determined runoff, sediment, dissolved reactive phosphorus (DRP) in a 0.45-microm filtered sample, and FeO-P and total P in unfiltered samples. Soil surface conditions had no effect on P runoff relationships. Water source had no significant effect on the relationship between DRP or FeO-P runoff and soil test P, except for DRP in RO runoff versus water-soluble soil P (r2 = 0.90). Total P in RO runoff versus soil P were not related; but weakly correlated for RO/Tap (r2 < 0.50). Water source and soil surface conditions had little or no effect on P runoff from this calcareous soil.

Phosphorus losses in furrow irrigation runoff.

Phosphorus (P) often limits the eutrophication of streams, rivers, and lakes receiving surface runoff. We evaluated the relationships among selected soil P availability indices and runoff P fractions where manure, whey, or commercial fertilizer applications had previously established a range of soil P availabilities on a Portneuf silt loam (coarse-silty, mixed, superactive, mesic Durinodic Xeric Haplocalcid) surface-irrigated with Snake River water. Water-soluble P, Olsen P (inorganic and organic P), and iron-oxide impregnated paper-extractable P (FeO-Ps) were determined on a 0.03-m soil sample taken from the bottom of each furrow before each irrigation in fall 1998 and spring 1999. Dissolved reactive phosphorus (DRP) in a 0.45-microm filtered runoff sample, and iron-oxide impregnated paper-extractable P (FeO-Pw), total P, and sediment in an unfiltered runoff sample were determined at selected intervals during a 4-h irrigation on 18.3-m field plots. The 1998 and 1999 data sets were combined because there were no significant differences. Flow-weighted average runoff DRP and FeO-Pw concentrations increased linearly as all three soil P test concentrations increased. The average runoff total P concentration was not related to any soil P test but was linearly related to sediment concentration. Stepwise regression selected the independent variables of sediment, soil lime concentration, and soil organic P extracted by the Olsen method as related to average runoff total P concentration. The average runoff total P concentration was 1.08 mg L(-1) at a soil Olsen P concentration of 10 mg kg(-1). Soil erosion control will be necessary to reduce P losses in surface irrigation runoff.

Getting it all together. Systems should link their strategic and financial planning.

Foreseeing dramatic changes in healthcare delivery, the leaders of the Franciscan Health System (FHS) decided in the early 1990s to more closely link their strategic and financial planning. Though this cooperation was tentative at first, by 1993 both our planners and our chief financial officers shared certain assumptions about the future--above all, that the coming delivery model was managed care provided by integrated delivery systems (IDSs). Having agreed on our assumptions, we translated them into a vision statement, from which we derived four strategic goals: Advance the healing mission of our sponsors; Create a culture of continuous improvement in leadership, quality, innovation, cost-effectiveness, and measurable customer value; Create an environment that values and empowers those with whom we work; Develop, through partnering, an IDS that provides affordable care to our communities; Our goals established, we charted what we call a "crosswalk" between the strategic and financial aspects of our budgeting. We found that we had to think in a new way about capital. For example, we began investing as heavily in "soft" items like research, partnerships, and new services as in the traditional "bricks and mortar." This process is new for us, and developing it has not always been comfortable. But we believe it has helped us to more wisely allocate FHS's resources and thus give our system greater stability.